Preparation of both enantiomers of cyclopropane derivatives from the reaction of vinyl selenones with di-(-)-bornyl malonate

Article abstract of DOI:10.1016/j.tetasy.2009.05.019

The reaction of vinyl selenones with di-(-)-bornyl malonate and sodium hydride occurred with low diastereoselectivity and afforded a mixture of two diastereomeric cyclopropane derivatives in comparable yields. These, however, could be easily separated by chromatography. Removal of the bornyl group afforded highly enantiomerically enriched cyclopropanes. An example of the simple conversions of these cyclopropanes into useful cyclopropane α-amino acids is also illustrated. The syntheses of several vinyl selenides and selenones are also described.

Full text of DOI:10.1016/j.tetasy.2009.05.019

Tetrahedron: Asymmetry 20 (2009) 1506–1514
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Preparation of both enantiomers of cyclopropane derivatives
from the reaction of vinyl selenones with di-(ꢀ)-bornyl malonate
*
*
Luana Bagnoli , Catalina Scarponi, Lorenzo Testaferri, Marcello Tiecco
Dipartimento di Chimica e Tecnologia del Farmaco, Sezione di Chimica Organica, Università di Perugia, 06123 Perugia, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
The reaction of vinyl selenones with di-(ꢀ)-bornyl malonate and sodium hydride occurred with low dia-
stereoselectivity and afforded a mixture of two diastereomeric cyclopropane derivatives in comparable
yields. These, however, could be easily separated by chromatography. Removal of the bornyl group affor-
ded highly enantiomerically enriched cyclopropanes. An example of the simple conversions of these
Received 5 May 2009
Accepted 20 May 2009
Available online 26 June 2009
cyclopropanes into useful cyclopropane
a
-amino acids is also illustrated. The syntheses of several vinyl
selenides and selenones are also described.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
some cases, the di-(ꢀ)-menthyl malonate. Owing to the structure
of the starting selenones (Scheme 1), the cyclization reaction will
create a new stereogenic center and thus will give rise to a mixture
of two enantiomerically pure diastereoisomers.
The construction of chiral non-racemic cyclopropanes has
played a prominent role in organic synthesis, because the cyclopro-
pane unit is present in a number of useful natural and unnatural
products.1 Currently more than one hundred natural cyclopropanes
are known to be therapeutically active.2 In addition, chiral non-
racemic cyclopropanes are used as synthons in the synthesis of
more complex structures.3 Numerous synthetic procedures for the
preparation of optically active cyclopropanes have been developed.4
The most generally used methods are Simmons–Smith-type reac-
tions and the metal-catalyzed decomposition of diazo compounds
in the presence of alkenes.4 Another interesting approach is the
Michael initiated ring closure (MIRC) reaction, which involves a
conjugate addition to an electrophilic alkene to produce an enolate
which then undergoes an intramolecular ring closure.4a In previous
work carried out by Kuwajima et al.5a–c and by our group5d it has
been reported that the treatment of vinyl selenones with methylen-
ic compounds in basic media leads to the formation of cyclopro-
panes via an addition–substitution reaction (MIRC) (Scheme 1).
The selenone group activates the carbon–carbon double bond
toward the addition of anionic reagents while at same time acts
as a good leaving group in the following cyclization reaction.
The great leaving ability of the selenone group both in intermo-
lecular6a,b and in intramolecular6c,d nucleophilic substitutions is
well documented.
SeO2Ph
R
X
NaH
+
Y
R
X
Y
Scheme 1.
2. Results and discussion
The aryl vinyl phenyl selenones 3a–d necessary for the present
investigation were synthesized starting from the corresponding b-
bromostyrenes 1a–d. These were converted into the corresponding
aryl vinyl phenyl selenides (2a–d) which were then oxidized
(Scheme 2, Table 1).
Bromide 1a is commercially available. The (E)-bromides 1b–d
were obtained according to the procedure reported in the litera-
ture starting from cinnamic acids7 while the (Z)-bromide 1d was
obtained from anti-2,3-dibromo-3-(4-methoxyphenyl)propanoic
acid by microwave-induced debrominative decarboxylation.8
Although various methods are reported for the preparation of aryl
vinyl phenyl selenides,9 because of their importance in synthetic
organic chemistry, most of them involve the use of expensive cat-
alysts or starting materials, which are not readily available. Herein
we have employed the previously described10 vinylic substitution
of the bromides with phenyl selenide anion in dimethylformamide
(Scheme 2).
Herein we report the results of an investigation aimed at the
preparation of chiral non-racemic cyclopropanes using the
above-described reaction of vinyl selenones with malonates. For
this purpose, we have employed di-(ꢀ)-bornyl malonate, and in
* Corresponding authors. Tel.: +39 075 5855100; fax: +39 075 5855116 (M.T.).
E-mail addresses: bagnoli@unipg.it (L. Bagnoli), tiecco@unipg.it (M. Tiecco).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.05.019

L. Bagnoli et al. / Tetrahedron: Asymmetry 20 (2009) 1506–1514
1507
Ar
Ar
Ar
(PhSe)2,NaBH4
DMF, 120°C
MCPBA
CH2Cl2
Br
SeO2Ph
3a-d
SePh
2a-d
1a-d
Scheme 2.
Interestingly, the formation of aryl vinyl phenyl selenides 2a–d
occurs with complete retention of configuration.10 The subsequent
oxidation of these selenides 2a–d was carried out using m-chloro-
perbenzoic acid (MCPBA).5d The (E)-vinyl selenones 3a–d were ob-
tained in good yields, whereas (Z)-vinyl selenone 3d was formed in
moderate yield even with a large excess of MCPBA (Table 1).
The di-(ꢀ)-bornyl malonate 5 or the di-(ꢀ)-menthyl malonate11
50 was easily prepared starting from malonyl dichloride and [(1S)-
endo]-(ꢀ)-borneol or (1R,2S,5R)-(ꢀ)-menthol, respectively, in the
presence of Et3N.
As indicated in Scheme 4, the Michael initiated ring closure
(MIRC) reactions of the selenones 3a–f with the enolate ions of
the di-(ꢀ)-bornyl malonate 5 or of the di-(ꢀ)-menthyl malonate
50 were carried out to initially give the carbanions 7a–e or 70a,
70f, which then suffered a proton transfer to 8a–e, or 80a, 80f. The
intramolecular displacement of the PhSeO2 group by these anions
afforded a mixture of the two diastereoisomeric cyclopropane
derivatives 9a–e, 10a–e or 90a, 100a or 90f, 100f.
The first experiment was carried out with the styryl phenyl sel-
enone 3a (Table 3, entry 2) and the di-(ꢀ)-menthyl malonate 50.
This reaction was not diastereoselective, since it afforded a 1:1
mixture (by NMR) of two diastereomeric cyclopropane derivatives
90a and 100a. In the search for a better diastereoselectivity the reac-
tion was repeated using the di-(ꢀ)-bornyl malonate 5 (Table 3, en-
try 1). Unfortunately in this case, the selectivity was very low with
the two cyclopropanes 9a and 10a being obtained in a ratio of
31:69 (by NMR). TLC analysis of the reaction mixtures showed that
the two diastereoisomers gave two well-separated spots. Thus,
these mixtures were submitted to medium pressure column chro-
matography. In this way, we could obtain both diastereoisomers in
an almost pure form. The chromatographic separation was more
efficient in the case of the bornyl malonate than in that of the men-
thyl malonate derivatives (Table 3, entries 1 and 2).
The possibility of effecting a simple preparation of both diaste-
reoisomers of the cyclopropane derivatives and hence, after sepa-
ration and removal of the chiral alcoholic moiety, both the
enantiomers in an highly enriched form, induced us to carry out
further experiments with other vinyl selenones using the malonate
5.
It is interesting to note that, starting from selenones (E)-3d and
(Z)-3d the same mixture of the two cyclopropane diastereoisomers
9d and 10d was obtained (Table 3, entries 5 and 6). In the light of
these results the cyclization reactions of the alkyl vinyl phenyl sel-
enones 3e and 3f were effected on the E- and Z-mixture (Table 3,
entries 7 and 8).
Table 1
Bromide
R
Selenide
Yield (%)
Selenone
Yield (%)
(E)-1a
(E)-1b
(E)-1c
(E)-1d
(Z)-1d
Ph
(E)-2a
(E)-2b
(E)-2c
(E)-2d
(Z)-2d
94
94
72
77
76
(E)-3a
(E)-3b
(E)-3c
(E)-3d
(Z)-3d
90
60
67
63
40
4-ClC6H4
4-MeC6H4
4-MeOC6H4
4-MeOC6H4
The same reagent was also employed for the oxidations of the
alkyl vinyl phenyl selenides 2e,f. These were synthesized by the
one-pot Markovnikov addition of phenylselenyl bromide to the cor-
responding alkenes 4e,f followed by treatment with t-BuOK
(Scheme 3).9b These alkyl selenides were obtained as a mixture
of E- and Z-stereoisomers. The selenones 3e and 3f were therefore
also obtained as a mixture of E- and Z-isomers (Table 2).
R
Br
2.t-BuOK
1.PhSeBr
CH2Cl2
RCCH2SePh
THF
4e,f
R
R
MCPBA
CH2Cl2
SePh
SeO2Ph
2e,f
3e,f
Scheme 3.
In the case of 3e, the chromatographic separation of the two
reaction products was very poor and therefore this reaction was
not further investigated. In all the other cases, the mixture of the
two diastereoisomeric cyclopropanes produced was well separated
by medium pressure column chromatography. The reaction of 3f
was more conveniently carried out using the di-(ꢀ)-menthyl mal-
Table 2
Alkene
R
Selenide (E:Z)
Yield (%)
Selenone (E:Z)
Yield (%)
4e
4f
PhCH2OCH2
C6H13
2e (33:67)
2f (50:50)
60
84
3e (33:67)
3f (50:50)
67
77
R
R
2
R
SeO2Ph
R
SeO2Ph
3
3
2
R
R*O2C
R*O2C
NaH
R*O2C
R*O2C
1
1
R*O2C
CO2R*
R*O2C
CO2R*
CO2R*
CO2R*
SeO2Ph
3a-f
9a-e
9'a,9'f
8a-e
8'a,8'f
10a-e
10'a,10'f
7a-e
7'a,7'f
5': R*=
(-)-Menthyl
5: R*=
(-)-Bornyl
Scheme 4.

1508
L. Bagnoli et al. / Tetrahedron: Asymmetry 20 (2009) 1506–1514
Table 3
Entries
Selenones 3a–f
Cyclopropanes 9 and 10 (R* = bornyl) or 90 and 100 (R* = menthyl)
R
E:Z
Yieldsa (%)
Diastereomeric ratiob (dr)
9 or 90 Config.,c drd
10 or 10’ Config.,c drd
1
2
3
4
5
6
7
8
a: Ph
a: Ph
b: 4-Cl–C6H4
c: 4-Me–C6H4
d: 4-MeO–C6H4
E
E
E
E
E
Z
83
77
85
68
67
65
73
86
9a:10a = 31:69
90a:100a = 50:50
9b:10b = 30:70
9c:10c = 50:50
9d:10d = 42:58
9d:10d = 42:58
9e:10e = 50:50
90f:100f = 50:50
(R)-9a, 98:2
(R)-90a 98:2
(R)-9b, 96:4
(R)-9c, 99:1
(R)-9d, 91:9
(S)-10a, 98:2
(S)-100a, 87:13
(S)-10b, 96:4
(S)-10c 98:2
(S)-10d 97:3
e: PhCH2OCH2
f: C6H13
33:67
50:50
90f, 99:1
100f, 99:1
a
Determined on isolated products after column chromatography.
Determined before chromatography by 1H NMR of the reaction mixtures.
Configuration of carbon 2 of cyclopropane.
b
c
d
Dr of product obtained after medium pressure column chromatography. The dr was deduced from the ee of the enantiomers obtained after removal of the bornyl or
menthyl groups (see Table 4).
onate 50 rather than 5. The results of all the cyclization reactions
investigated are collected in Table 3.
reduced instead with lithium aluminum hydride to afford the cor-
responding diols 13c,d and ent-13c,d (Scheme 5) whose enantio-
meric excesses were determined by HPLC (Table 4). The
diastereoisomers 9a, 90f and 10a, 100f were also converted into
the corresponding diols 13a,f and ent-13a,f (Scheme 5 and Table 4).
The absolute configurations of the newly generated stereogenic
centers in compounds 12a,b and ent-12a,b were determined by
comparison of their optical properties with those reported in the
literature.13a–f The signs of the specific rotations of 12a,b are posi-
tive while those of ent-12a,b are negative (Table 4). These attribu-
tions are in agreement with the assumption reported in the
literature according to which the specific rotation values of a series
of 2-phenylcyclopropanecarboxylic acids derivatives the (R)-iso-
mers have a positive sign and the (S)-isomers have a negative
sign.13b,f
In order to determine the diastereomeric purity (Table 3) of the
two diastereoisomers isolated by column chromatography and the
absolute configurations of the newly generated stereogenic center
at the 2 position of the cyclopropanes, the bornyl or menthyl
groups were removed. For this purpose, compounds 9a,b, 90f and
10a,b, 100f were converted into the corresponding dimethyl esters
12a,b,f and ent-12a,b,f (Scheme 5).
These conversions could not be effected by direct transesterifi-
cation. The bornyl esters were therefore hydrolyzed with sodium
hydroxide in the presence of hydroquinone to give acids 11a,b,f
and ent-11a,b,f which were then directly treated with diazometh-
ane12 without isolation (Scheme 5). The enantiomeric excesses of
cyclopropanes 12a,b,f and ent-12a,b,f were determined by HPLC
analysis on a chiral column (Table 4). The hydrolysis of cyclopro-
panes 9c,d and 10c,d did not give clean reaction mixtures so the
methyl esters were not prepared. Compounds 9c,d and 10c,d were
The absolute configurations of the 2-aryl-substituted cyclopro-
pane diols 13c,d and ent-13c,d are proposed to be the same as
those of the methyl esters 12a,b and ent-12a,b. In fact it seems
R
R
CH2N2
R
NaOH
MeO2C
12a,b,f
CO2Me
HO2C
CO2H
Hydroquinone
11a,b,f
R*O2C
CO2R*
9a-d,9'f
R
LiAlH4
HOH2C
CH2OH
13a,c,d,f
R
R
CH2N2
R
NaOH
HO2C
CO2H
MeO2C
CO2Me
Hydroquinone
ent-11a,b,f
ent-12a,b,f
R*O2C
CO2R*
10a-d,10'f
R
LiAlH4
HOH2C
CH2OH
ent-13a,c,d,f
The absolute configuration of compounds f was not determined
Scheme 5.

L. Bagnoli et al. / Tetrahedron: Asymmetry 20 (2009) 1506–1514
Methyl esters 12, ent-12 and diols 13, ent-13
1509
Table 4
Entries
Starting products
Reaction products
Yields (%)
Ee (%)
Conf.
[a]
1
2
3
4
5
6
7
8
9a
10a
9a
10a
9b
10b
12a
ent-12a
13a
ent-13a
12b
ent-12b
13c
ent-13c
13d
ent-13d
12f
ent-12f
13f
53
51
92
85
50
45
88
83
94
72
56
70
83
93
96
96
96
96
92
92
98
96
82
94
98
98
98
98
(R)
(S)
(R)
(S)
(R)
(S)
(R)
(S)
(R)
(S)
+121.7
ꢀ114.3
+2.2
ꢀ2.1
+123.3
ꢀ117.2
+9.9
9c PhCH2OCH2
10c
9d
ꢀ8.6
9
+9.1
10
11
12
13
14
10d
ꢀ9.4
90f
+53.0
ꢀ49.0
+35.8
ꢀ33.8
100f
90f
100f
ent-13f
reasonable to assume so since neither the hydrolysis nor the reduc-
tion reactions involve the carbon 2 of the cyclopropane ring.
The absolute configuration of 2-alkyl-substituted cyclopropanes
12f, ent-12f, 13f and ent-13f could not be assigned.
4. Experimental
All new compoundswere characterized by GC–MS and 1H and 13
C
NMR spectra. GC analyses and MS spectra were carried out with an
HP 6890 gas chromatograph (25 m dimethyl silicone capillary col-
umn) equipped with an HP 5973 Mass Selective Detector; for the
ions containing selenium, only the peaks arising from the sele-
nium-80 isotope are given. 1H and 13C NMR spectra were recorded
at 400 and 100.62 MHz, respectively, on a Bruker DRX 400 instru-
ment; CDCl3 was used as the solvent and TMS as the standard. FT-
IR spectra were recorded with a Jasco model 410 spectrometer. HPLC
analyses were performed on an HP 1100 instrumentequipped with a
chiral column and an UV detector. Optical rotations were measured
with a Jasco DIP-1000 digital polarimeter. Elemental analyses were
carried out on a Carlo Erba 1106 Elemental Analyzer.
Of particular importance is the possibility of converting chiral
non-racemic cyclopropanes into cyclopropane
a-amino acids
(ACCs) since these compounds present various biological activities
as low molecular weight inhibitors or as non-proteogenic compo-
nents in peptides.14 Several methods have been reported in the lit-
erature for their preparation,15 yet few methods are available for a
simple preparation of differently substituted cyclopropane deriva-
tives from readily available starting materials.
Starting from our enantiomerically enriched cyclopropanes,
ACCs could be easily synthesized through a few simple steps.13c,16
Thus, cyclopropanes 12a and ent-12a were converted into the BOC-
protected amino esters 14a and ent-14a via hydrolysis of the least
encumbered ester functionality followed by a Curtius rearrange-
ment (Scheme 6). The specific rotations of these two products
are in agreement with those reported in the literature.13c
4.1. Starting products
Commercial (1R,2S,5R)-(ꢀ)-menthol (ee 99%) and [(1S)-endo]-
(ꢀ)-borneol (ee 99%), vinyl bromide 1a, and alkenes 4e,f were used
without further purification. The bromides 1b–d were synthesized
according to the procedure described in the literature7,8 (see Table
1). Di-(ꢀ)-menthyl malonate was prepared as described in the
literature.11
Ph
(R)
MeO2C
Ph
(R)
a) NaOH, MeOH
b) N3PO(OPh)2,
NEt3, t-BuOH, 95°C
MeO2C (S) NHBOC
CO2Me
CO2Me
4.2. Synthesis of aryl vinyl phenyl selenides
(R)-12a
(1S,2R)-14a (85%)
Ph
(S)
MeO2C
Ph
(S)
Selenide 2a was synthesized according to the procedure re-
ported in the literature.10
Sodium borohydride (6 mmol) was added to a solution of diphe-
nyl diselenide (3 mmol) in dimethylformamide (8 mL) at 120 °C.
After 45 min, a solution of the vinyl bromides 1b–d was added.
The progress of the reactions was monitored by TLC and by GC–
MS. After 5 h the reaction mixtures were poured into aqueous
NH4Cl solution and extracted with diethyl ether. The organic layers
were washed with water and brine, dried over Na2SO4, filtered, and
evaporated under vacuum. Reaction products were obtained in a
pure form after column chromatography of the residue on silica
gel using light petroleum as eluant. Reaction products and reaction
yields are reported in Scheme 2 and in Table 1. The physical and
spectroscopic data of compounds 2b–d are reported below.
(R)
MeO2C
NHBOC
(1R,2S)-ent-14a (65%)
(S)-ent-12a
Scheme 6.
3. Conclusions
In conclusion the results reported in this paper illustrate a con-
venient approach for the synthesis of highly enantiomerically
enriched cyclopropanes using vinyl selenones and chiral non-race-
mic methylenic compounds. It is shown that these cyclopropanes
can be conveniently employed for the preparation of cyclopropane
4.2.1. (E)-2-(4-Chlorophenyl)vinyl phenyl selenide, 2b
Oil; 1H NMR (400 MHz, CDCl3, 25 °C, TMS): d 7.65–7.51 (m, 2H),
7.36–7.32 (m, 3H), 7.30–7.24 (m, 4H), 7.18 (d, 1H, J = 15.8 Hz), 6.79
(d, 1H, J = 15.8 Hz); 13C NMR (100 MHz, CDCl3, 25 °C, TMS): d 135.4,
133.2, 133.1, 132.8 (two carbons), 129.6, 129.5 (two carbons),
a-amino acids. The biological study of the new amino acids, as well
as of their effect on the structure of peptides and proteins, is a
central goal in drug discovery.14,17

1510
L. Bagnoli et al. / Tetrahedron: Asymmetry 20 (2009) 1506–1514
128.8 (two carbons), 127.6, 127.1 (two carbons), 120.6; GC–MS
(70 eV, EI): m/z (rel. int.): 294 (92), 259 (19), 214 (100), 178 (93),
165 (11), 102 (37), 75 (22), 51 (20). Anal. Calcd for C14H11ClSe: C,
57.26; H, 3.78. Found: C, 57.31; H, 3.81.
second peak, (E): 304 (25),198 (7), 185 (26), 183 (22), 157 (32),
115 (28), 104 (27), 91 (100), 77 (27), 65 (21).
4.3.2. [(1E) and (1Z)-Oct-1-en-1-ylseleno]benzene, 2f
Oil; 1H NMR (400 MHz, CDCl3, 25 °C, TMS): d 7.53–7.48 (m,
4H), 7.33–7.27 (m, 6H), 6.48 (dt, 1H, J = 1.3, 8.9 Hz, Z), 6.43 (dt,
1H, J = 1.4, 15.1 Hz, E), 6.16 (dt,, 1H, J = 6.9, 15.1 Hz, E), 6.10 (dt,
1H, J = 7.1, 8.8 Hz, Z), 2,23 (dquart, 2H, J = 1.1, 8.0 Hz, Z), 2,19
(dquart, 2H, J = 1.1, 8.0 Hz, E), 1.51–1.45 (m, 4H), 1.41–1.29 (m,
12H), 0.94 (t, 6H, J = 6.7 Hz); 13C NMR (100 MHz, CDCl3, 25 °C,
TMS): d: (mix E:Z): 140.7, 135.4, 131.7 (two carbons), 131.4,
131.3 (two carbons), 129.1 (four carbons), 126.9, 126.7, 126.6,
120.0, 115.8, 34.3, 31.7, 31.6, 31.2, 28.9 (two carbons), 28.8,
28.7, 22.6 (two carbons), 14.1 (two carbons); GC–MS (70 eV,
EI): m/z (rel. int.) first peak: 268 (62), 195 (16), 158 (23), 117
(61), 116 (100), 91 (22), 77 (24), 55 (23); second peak: 268
(61), 195 (17), 158 (21), 117 (57),116 (100), 91 (21), 77 (21),
55 (19).
4.2.2. (E)-2-(4-Methylphenyl)vinyl phenyl selenide, 2c
Oil, 1H NMR (400 MHz, CDCl3, 25 °C, TMS): d 7.57–7.52 (m, 2H),
7.35–7.29 (m, 3H), 7.25–7.22 (m, 2H), 7.15–7.09 (m, 3H), 6.90 (d,
1H, J = 15.7 Hz), 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3, 25 °C,
TMS): d 137.5, 135.5, 134.1, 132.1 (two carbons), 130.4, 129.3
(two carbons), 129.2 (two carbons), 127.1, 125.9 (two carbons),
117.7, 21.1; MS (70 eV, EI): m/z (rel. int.): 274 (98), 272 (66), 259
(36), 194 (100), 179 (85), 169 (25), 115 (72), 91 (33), 77 (23), 65
(19), 51 (20). Anal. Calcd for C15H14Se: C, 65.94; H, 5.16. Found:
C, 65.91; H, 5.27.
4.2.3. (E)-2-(4-Methoxyphenyl)vinyl phenyl selenide, 2d
Oil; 1H NMR (400 MHz, CDCl3, 25 °C, TMS): d 7.57–7.54 (m, 2H),
7.35–7.27 (m, 5H), 7.04 (d, 1H, J = 15.7 Hz), 6.93–6.86 (m, 3H), 3.83
(s, 3H); 13C NMR (100 MHz, CDCl3, 25 °C, TMS): d 159.2, 135.7,
131.8 (two carbons), 130.7, 129.7, 129.1 (two carbons), 127.2
(two carbons), 126.9, 115.8, 113.7 (two carbons), 55.4; GC-MS
(70 eV, EI): m/z (rel. int.): 290 (M+, 46), 210 (100), 195 (29), 165
(26), 89 (21), 77 (17). Anal. Calcd for C15H14OSe: C, 62.29; H,
4.88. Found: C, 62.33; H, 4.92.
4.4. Synthesis of vinyl phenyl selenones
The oxidation of the selenides 2a–f (1 mmol) was carried out in
dichloromethane (4 mL) and methanol (4 mL) at room temperature
using MCPBA (4 mmol) as oxidant. The progress of the reactions
was monitored by TLC. The reaction mixture was poured onto
10% Na2CO3 solution, and extracted with diethyl ether. The organic
layers were washed with water, dried, and evaporated. The residue
was chromatographed through a deactivated silica gel column
using a mixture of dichloromethane and methanol (99:1) as elu-
ant; for the selenone 3e the crude mixture was directly used. Reac-
tion products and reaction yields are reported in Schemes 2 and 3
and in Tables 1 and 2. The physical and spectroscopic data of sele-
none 3a were identical to those reported in the literature.5d The
physical and spectroscopic data of compounds 3b–f are reported
below.
4.2.4. (Z)-2-(4-Methoxyphenyl)vinyl phenyl selenide, 2d
Mp 66–69 °C 1H NMR (400 MHz, CDCl3, 25 °C, TMS): d 764–7.55
(m, 2H), 7.42–7.27 (m, 6H), 6.97–6.93 (m, 2H), 6.67 (d, 1H,
J = 10.3 Hz), 3.85 (s, 3H); 13C NMR (100 MHz, CDCl3, 25 °C, TMS):
d 158.6, 132.7 (two carbons), 131.6, 129.8, 129.7, 129.6 (two car-
bons), 129.1, (two carbons), 127.3, 121.0, 113.7 (two carbons),
53.4 GC–MS (70 eV, EI): m/z (rel. int.): 290 (M+, 63), 210 (100),
195 (29), 165 (26), 89 (21), 77 (17). Anal. Calcd for C15H14OSe: C,
62.29; H, 4.88. Found: C, 62.35; H, 4.97.
4.3. Synthesis of alkyl vinyl phenyl selenides
4.4.1. (E)-2-(4-Chlorophenyl)vinyl phenyl selenone, 3b
Mp 152–153 °C; 1H NMR (400 MHz, CDCl3, 25 °C, TMS): d 8.01–
7.99 (m, 2H), 7.85 (d, 1H, J = 15.4 Hz), 7.72–7.62 (m, 3H), 7.47–7.45
(m, 2H), 7.40–7.38 (m, 2H), 7.19 (d, 1H, J = 15.4 Hz); 13C NMR
(100 MHz, CDCl3, 25 °C, TMS): d 143.7, 141.7, 137.8, 134.1, 130.1
(two carbons), 129.8, 129.7 (two carbons), 129.4 (two carbons),
127.8, 126.6 (two carbons); FT-IR (HTAR): 936 and 881 cmꢀ1
(SeO2). Anal. Calcd for C14H11ClO2Se: C, 51.64; H, 3.40. Found: C,
51.84; H, 3.55.
Phenylselenyl bromide (1.2 mmol) was added to a solution of
alkenes 4e, 4f (1 mmol) in dry dichloromethane (8 mL) at room
temperature and in acetonitrile (8 mL) at 80 °C, respectively. After
4 h, the reaction mixtures were directly evaporated. To the result-
ing residues potassium tert-butoxide9b (2 mmol) in tetrahydrofu-
ran (8 mL) was added and the mixtures were allowed to stand
for 1 h at room temperature. The reaction mixtures were poured
into aqueous NH4Cl solution and extracted with diethyl ether.
The organic layers were dried over Na2SO4, filtered, and evaporated
under vacuum. The residues were chromatographed through a sil-
ica gel column using hexane as eluant. Reaction products and reac-
tion yields are reported in Scheme 3 and in Table 2. The physical
and spectroscopic data of compounds 2e,f are reported below.
4.4.2. (E)-2-(4-Methylphenyl)vinyl phenyl selenone, 3c
Mp 145–148 °C; 1H NMR (400 MHz, CDCl3, 25 °C, TMS): d 7.94–
7.91 (m, 2H), 7.78 (d, 1H, J = 15.4 Hz), 7.63–7.53 (m, 3H), 7.33 (d,
2H, J = 8.0 Hz), 7.14 (d, 2H, J = 8.0 Hz), 7.03 (d, 1H, J = 15.4 Hz),
2.31 (s, 3H); 13C NMR (100 MHz, CDCl3, 25 °C, TMS): d 145.1,
142.4, 142.1, 133.9, 130.0 (two carbons), 129.7 (two carbons),
128.6, 128.5 (two carbons), 126.6 (two carbons), 126.0, 21.4; FT-
IR (HTAR): 935 and 882 cmꢀ1 (SeO2). Anal. Calcd for C15H14O2Se:
C, 59.02; H, 4.62. Found: C, 59.14; H, 4.75.
4.3.1. {[(1E) and {[(1Z)-3-(Benzyloxy)prop-1-en-1-
yl]seleno}benzene, 2e
Oil; 1H NMR (400 MHz, CDCl3, 25 °C, TMS): d 7.46–7.39 (m, 4H),
7.35–7.18 (m, 16H), 6.70–6.60 (m, 2H), 6.18 (dt, 1H, J = 5.9, 9.3 Hz,
Z), 6.03 (dt, 1H, J = 5.9, 15.0 Hz, E), 4.50 (s, 2H, Z), 4.46 (s, 2H, E),
4.14–4.09 (m, 2H, Z), 4.01–3.96 (dd, 2H, E); 13C NMR (100 MHz,
CDCl3, 25 °C, TMS): d: 138.0 (two carbons), 132.8, 132.1 (two car-
bons), 132.0, 131.0 (two carbons), 130.0 (two carbons), 129.3
(two carbons), 129.2 (two carbons), 128.4 (four carbons), 127.8
(two carbons), 127.7, 127.6 (two carbons), 127.4, 127.2 (two car-
bons), 124.5, 121.9, 72.4, 72.1, 70.9, 68.4; GC-MS (70 eV, EI): m/z
(rel. int.): first peak, (Z): 304 (12), 198 (67), 195 (22), 194 (18),
183 (36), 157 (26), 117 (25), 104 (27), 91 (100), 77 (27), 65 (21).
4.4.3. (E)-2-(4-Methoxyphenyl)vinyl phenyl selenone, 3d
Mp 145–148 °C; 1H NMR (400 MHz, CDCl3, 25 °C, TMS): d 8.02–
8.00 (m, 2H), 7.83 (d, 1H, J = 15.4 Hz), 7.71–7.61 (m, 3H), 7.48 (d,
2H, J = 8.8 Hz), 7.01 (d, 1H, J = 15.4 Hz), 6.94 (d, 2H, J = 8.8 Hz),
3.85 (s, 3H); 13C NMR (100 MHz, CDCl3, 25 °C, TMS): d 162.3,
144.7, 142.2, 133.8, 130.5 (two carbons), 130.0 (two carbons),
126.5 (two carbons), 124.1, 123.9, 114.5 (two carbons), 55.3; FT-
IR (HTAR): 930 cmꢀ1 and 881 cmꢀ1. Anal. Calcd for C15H14O3Se:
C, 56.08; H, 4.39. Found: C, 56.19; H, 4.45.

L. Bagnoli et al. / Tetrahedron: Asymmetry 20 (2009) 1506–1514
1511
4.4.4. (Z)-2-(4-Methoxyphenyl)vinyl phenyl selenone, 3d
Mp 136–139 °C; 1H NMR (400 MHz, CDCl3, 25 °C, TMS): d 7.90–
7.87 (m, 2H), 7.72–7.69 (m, 2H), 7.61–7.57 (m, 1H), 7.52–7.48 (m,
2H), 7.40 (d, 1H, J = 10.4 Hz), 6.88–6.83 (m, 2H), 6.62 (d, 1H,
J = 10.4 Hz), 3.83 (s, 3H); 13C NMR (100 MHz, CDCl3, 25 °C, TMS):
d 161.5, 144.8, 142.1, 133.6, 132.3 (three carbons), 129.6 (two car-
bons), 126.4 (two carbons), 123.8, 113.7 (two carbons), 55.1; FT-IR
(HTAR): 932 and 880 cmꢀ1. Anal. Calcd for C15H14O3Se: C, 56.08; H,
4.39. Found: C, 56.19; H, 4.45.
ran (4 mL) was added (Table 3). The progress of the reactions (from
2 h to 8 h) was monitored by TLC. The reaction mixtures were
poured into aqueous NH4Cl solution and extracted with diethyl
ether. The organic layers were dried over Na2SO4, filtered, and
evaporated under vacuum. The diastereoisomeric cyclopropanes
9a–e, 10a–e and 90a, 100a, 90f, 100f were separated by medium
pressure chromatography on a silica gel column (Merk, LiChro-
prepÒ Si60, 40–63
lm) using a mixture of diethyl ether and light
petroleum as eluant (from 5:95 to 10:90). The separation of the
two diastereoisomers 9a and 10a, 9b and 10b, 9f and 10f could
be easily followed by TLC. The separation of diastereoisomers 9c
and 10c, 9d and 10d, which by TLC presented the same retention
times, was instead monitored by 1H NMR. The reaction products
and the reaction yields are reported in Scheme 4 and in Table 3.
Physical and spectroscopic data are reported below.
4.4.5. {[(1E) and {[(1Z)-3-(Benzyloxy)prop-1-en-1-yl]selenonyl}-
benzene, 3e
Oil; 1H NMR (400 MHz, CDCl3, 25 °C, TMS): d 7.99–7.90 (m, 4H),
7.72–7.58 (m, 6H), 7.40–7.20 (m, 11H), 7.02 (dt, 1H, J = 2.2, 14.9 Hz,
E), 6.87 (dt, 1H, J = 5.4, 10.5 Hz, Z), 6.62 (dt, 1H, J = 2.0, 10.5 Hz, Z),
4.72–4.67(m, 2H), 4.59 (s, 2H, E), 4.51 (s, 2H, Z), 4.32–4.29 (m, 2H);
13C NMR (100 MHz, CDCl3, 25 °C, TMS): d 146.6, 145.7, 142.3,
141.1, 136.7, 136.6, 133.8 (two carbons), 133.7 (two carbons),
129.9 (two carbons), 129.8 (three carbons), 128.1 (two carbons),
128.0 (two carbons), 127.6, 127.5, 127.4 (two carbons), 127.3
(three carbons), 126.3, 125.8, 72.7 (E), 72.5 (Z), 67.5(E), 65.5 (Z);
FT-IR (HTAR): 938 and 882 cmꢀ1 (SeO2).
4.6.1. Di-(ꢀ)-bornyl-(2R)-2-phenylcyclopropane-1,1-dicarboxy-
late, 9
Mp 76–80 °C; ½a 2D2
ꢁ
¼ þ43:9 (c 2.20, CHCl3); 1H NMR (400 MHz,
CDCl3, 25 °C, TMS): d 7.30–7.15 (m, 5H), 5.06 (ddd, 1H, J = 2.0, 3.4,
9.9 Hz), 4.52 (ddd, 1H, J = 2.0, 3.4, 9.9 Hz), 3.23 (t, 1H, J = 8.8 Hz),
2.40 (ddt, 1H, J = 3.5, 8.2, 13.5 Hz), 2.22–2.10 (m, 1H), 2.17 (dd, 1H,
J = 5.1, 8.8 Hz), 1,96–1.86 (m, 1H), 1.79–1.50 (m, 6H), 1.34–1.23
(m, 2H), 1.14–1.03 (m, 3H), 0.93 (s, 3H), 0.88 (s, 3H), 0.85 (s, 3H),
0.80 (dd, 1H, J = 3.5, 13.8 Hz), 0.77 (s, 3H), 0.76 (s, 3H), 0.35 (s, 3H);
13C NMR (100 MHz, CDCl3, 25 °C, TMS): d 170.2, 166.7, 134.8, 128.4
(two carbons), 128.2 (two carbons), 127.2, 81.3, 81.2, 49.0, 48.4,
47.8, 47.6, 44.8, 44.6, 38.0, 36.3, 35.9, 31.7, 28.0, 27.8, 27.0, 26.7,
19.6, 19.5, 18.9, 18.8, 18.6, 13.5, 12.7; GC–MS (70 eV, EI): m/z (rel.
int.): 478 (M+ < 1%), 342 (2), 137 (100), 95 (17), 81 (57). Anal. Calcd
for C31H42O4: C, 77.79; H, 8.84; N. Found: C, 77.85; H, 8.93.
4.4.6. [(1E)-Oct-1-en-1-ylselenonyl]benzene and [(1Z)-oct-1-en-
1-ylselenonyl]benzene, 3f
Oil; 1H NMR (400 MHz, CDCl3, 25 °C, TMS): d 7.99–7.89 (m, 4H),
7.68–7.43 (m, 7H), 7.17 (dt, 1H, J = 6.7, 15.0 Hz, E), 6.70–6.50 (m,
2H), 2.64 (q, 2H, J = 6.7 Hz), 2.30 (q, 2H, J = 7.0 Hz), 1.60–1.10 (m,
16H), 0.82 (t, 3H, J = 6.7 Hz), 0.81 (t, 3H, J = 6.6 Hz); 13C NMR
(100 MHz, CDCl3, 25 °C, TMS): d 150.6, 150.4, 133.9 (four carbons),
132.5 (two carbons), 130.1 (four carbons), 129.7 (two carbons),
126.6, 126.5, 32.0, 31.2 (two carbons), 29.4, 28.5 (two carbons),
28.2, 27.2, 22.3 (two carbons), 13.8 (two carbons). FT-IR (HTAR):
938 and 882 cmꢀ1 (SeO2).
4.6.2. Di-(ꢀ)-bornyl-(2S)-2-phenylcyclopropane-1,1-dicarboxy-
late, 10a
Mp 127–130 °C;
½
a 2D2
ꢁ
¼ ꢀ113:9 (c 2.8, CHCl3); 1H NMR
4.5. Synthesis of di-(ꢀ)-bornyl malonate 5
(400 MHz, CDCl3, 25 °C, TMS): d 7.32–7.22 (m, 5H), 4.99 (ddd, 1H,
J = 3.5, 5.3, 9.9 Hz), 4.53 (ddd, 1H, J = 3.5, 5.3, 9.9 Hz), 3.20 (t, 1H,
J = 8.4 Hz), 2.40 (ddt, 1H, J = 3.5, 8.0, 13.7 Hz), 2.14 (dd, 1H,
J = 5.2, 8.4 Hz), 2.02–1.89 (m, 2H), 1.77–1.74 (m, 1H), 1.73–1.66
(m, 3H), 1.59–1.51 (m, 2H), 1.33–1.23 (m, 2H), 1.18–1.12 (m,
1H), 1.02 (dd, 1H, J = 3.4, 13.8 Hz), 0.92 (s, 3H), 0.88 (s, 6H), 0.84–
0.79 (m, 1H), 0.78 (s, 3H), 0.72 (s, 3H), 0.77 (s, 3H), 0.08 (dd, 1H,
J = 3.4, 13.9 Hz); 13C NMR (100 MHz, CDCl3, 25 °C, TMS): d 169.9,
166.8, 134.7, 128.4 (two carbons), 128.2 (two carbons), 127.2,
81.6, 81.4, 48.8, 48.3, 47.9, 47.4, 44.7, 44.4, 38.2, 36.7, 35.8, 31.5,
27.9, 27.4, 27.0, 26.9, 19.6, 19.5, 18.7, 18.6, 18.4, 13.6, 13.5; GC–
MS (70 eV, EI): m/z (rel. int.): 478 (M+ <1%), 342 (1), 171 (6), 137
(100), 81 (53), 69 (10). Anal. Calcd for C31H42O4: C, 77.79; H,
8.84; N. Found: C, 77.68; H, 8.71.
Malonyl dichloride (2 mmol) was slowly added to a stirred solu-
tion of Et3N (2 mmol) and (1S)-endo-(ꢀ)-borneol (4.5 mmol) in
CH2Cl2 (30 mL) at ꢀ78 °C under N2, and the resulting solution
was warmed at room temperature and stirred for 3 h. The reaction
was quenched slowly with NH4Cl and the aqueous layer was ex-
tracted with CH2Cl2. The organic phase was dried over sodium sul-
fate and the solvent was removed in vacuum. The residue was
chromatographed through a silica gel column using a mixture of
diethyl ether and light petroleum (3:97) as eluant. The physical
and spectroscopic data of compound
5 are as follows: oil;
½
a 2D2
ꢁ
¼ ꢀ46:3 (c 2.5, CHCl3); 1H NMR (400 MHz, CDCl3, 25 °C,
TMS): d 4.98 (ddd, 2H, J = 2.1, 3.4, 9.6 Hz), 3.41 (s, 2H), 2.43–2.35
(m, 2H), 1.93 (ddd, 2H, J = 5.3, 9.4, 13.2 Hz), 1.81–1.69 (m, 4H),
1.36–1.22 (m, 4H), 1.06 (dd, 2H, J = 3.4, 13.7 Hz), 0.92 (s, 6H),
0.89 (s, 6H), 0.87 (s, 6H); 13C NMR (100 MHz, CDCl3, 25 °C, TMS):
d 166.8 (two carbons), 81.1 (two carbons), 48.8 (two carbons),
47.8 (two carbons), 44.9 (two carbons), 42.1, 46.5 (two carbons),
27.9 (two carbons), 26.9 (two carbons), 19.6 (two carbons), 18.7
(two carbons), 13.4 (two carbons). GC–MS (70 eV, EI): m/z (rel.
int.): 376 (5), 154 (14), 137 (100), 121 (41), 109 (17), 95 (86), 93
(52), 81 (69), 69 (23), 67 (19), 55 (16). Anal. Calcd for C23H36O4:
C, 73.37; H, 9.64; Found: C, 73.45; H, 9.58.
4.6.3. Di-(ꢀ)-menthyl-(2R)-2-phenylcyclopropane-1,1-dicarbo-
xylate, 90a
Mp 66–70 °C; ½a 1D9
ꢁ
¼ þ34:6 (c 1.69, CHCl3); 1H NMR (400 MHz,
CDCl3, 25 °C, TMS): d 7.28–7.19 (m, 5H), 4.75 (dt, 1H, J = 4.4,
10.9 Hz), 4.44 (dt, 1H, J = 4.4, 10.9 Hz), 3.20 (t, 1H, J = 8.6 Hz),
2.15 (dd, 1H, J = 5.1, 8.6 Hz), 2.15–2.10 (m, 1H), 1.90 (dsept, 1H,
J = 4.2, 6.8 Hz), 1.87–1.78 (m, 1H), 1.71–1.66 (m, 2H), 1.61 (dd,
1H, J = 5.1, 8.6 Hz), 1.63–1.45 (m, 4H), 1.45–1.30 (m, 3H), 1.18–
0.96 (m, 3H), 0.94–0.87 (m, 2H), 0.93 (d, 3H, J = 6.5 Hz), 0.90 (d,
3H, J = 7.0 Hz), 0.85 (d, 3H, J = 6.58 Hz), 0.79–0.75 (m, 1H), 0.78
(d, 3H, J = 6.8 Hz), 0.63 (d, 3H, J = 6.8 Hz), 0.31 (d, 3H, J = 6.8 Hz);
13C NMR (100 MHz, CDCl3, 25 °C, TMS): d 169.7, 166.2, 134.7,
128.3 (two carbons), 128.2 (two carbons), 127.2, 75.8, 75.2, 47.2,
46.5, 40.8, 40.5, 38.5, 34.3, 34.1, 31.7, 31.4, 31.2, 26.3, 24.9, 23.5,
22.8, 22.0 (two carbons), 20.8, 20.7, 18.5, 16.4, 15.7; GC–MS
(70 eV, EI): m/z (rel. int.): 482 (M+< 1%), 344 (7), 207 (76), 206
4.6. Synthesis of cyclopropane derivatives
Sodium hydride (1.5 mmol) was added to a solution of di-(ꢀ)-
bornyl malonate
(1 mmol) in dry tetrahydrofuran (4 mL) at room temperature. After
5
(1 mmol) or di-(ꢀ)-menthyl malonate 50
30 min a solution of the selenones 3a–f (1 mmol) in tetrahydrofu-

1512
L. Bagnoli et al. / Tetrahedron: Asymmetry 20 (2009) 1506–1514
(98), 189 (33), 171 (34), 138 (60), 83 (100), 69 (40), 55 (54). Anal.
Calcd for C31H46O4: C, 77.14; H, 9.61. Found: C, 77.23; H, 9.76.
3H), 0.36 (s, 3H); 13C NMR (100 MHz, CDCl3, 25 °C, TMS): d 170.3,
166.9, 136.8, 131.7, 128.9 (two carbons), 128.3 (two carbons),
81.2, 81.1, 49.0, 48.5, 47.9, 47.6, 44.8, 44.6, 37.9, 36.3, 35.9, 31.6,
28.0, 27.8, 27.1, 26.8, 20.9, 19.7, 19.6, 18.9, 18.8, 18.7, 13.5, 12.6;
GC–MS (70 eV, EI): m/z (rel. int.): 492 (M+<1%), 356 (2), 185 (11),
137 (100), 136 (23), 95 (19), 81 (60), 69 (12), 67 (10). Anal. Calcd
for C32H44O4: C, 78.01; H, 9.00. Found: C, 78.12; H, 9.15.
4.6.4. Di-(ꢀ)-menthyl-(2S)-2-phenylcyclopropane-1,1-dicarbo-
xylate, 100a
Mp 108–111 °C;
½
a 1D8
ꢁ
¼ ꢀ86:0 (c 0.84, CHCl3); 1H NMR
(400 MHz, CDCl3, 25 °C, TMS): d 7.28–7.19 (m, 5H), 4.85 (dt, 1H,
J = 4.4, 10.8 Hz), 4.45 (dt, 1H, J = 4.4, 10.9 Hz), 3.17 (t, 1H,
J = 8.5 Hz), 2.17 (dd, 1H, J = 5.0, 8.0 Hz), 2.05–1.86 (m, 3H), 1.72
(dd, 1H, J = 5.0, 8.0 Hz), 1.72–1.64 (m, 2H), 1.65–1.09 (m, 13H),
0.93 (d, 3H, J = 7.0 Hz), 0.92 (d, 3H, J = 6.5 Hz), 0.86 (d, 3H,
J = 7.0 Hz), 0.83 (d, 3H, J = 6.9 Hz), 0.71 (d, 3H, J = 6.5 Hz), 0.66
(d, 3H, J = 6.9 Hz); 13C NMR (100 MHz, CDCl3, 25 °C, TMS): d
169.7, 166.3, 134.7, 128.8 (two carbons), 128.1 (two carbons),
127.3, 75.5, 75.3, 47.2, 46.8, 40.9, 39.8, 37.9, 34.2, 34.0, 32.9,
31.5, 31.1, 25.9, 25.1, 23.1, 22.5, 22.0, 21.8, 21.2, 21.0, 18.5,
16.1, 15.5; GC–MS (70 eV, EI): m/z (rel. int.): 482 (M+<1%), 344
(6), 207 (72), 206 (91), 189 (29), 171 (30), 138 (57), 83 (100), 69
(41), 55 (54). Anal. Calcd for C31H46O4: C, 77.14; H, 9.61;. Found:
C, 77.29; H, 9.72.
4.6.8. Di-(ꢀ)-bornyl-(2S)-2-(4-methylphenyl)cyclopropane-1,1-
dicarboxylate, 10c
Oil; ½a 2D6
ꢁ
¼ ꢀ104:2 (c 2.02, CHCl3); 1H NMR (400 MHz, CDCl3,
25 °C, TMS): d 7.12 (d, 2H, J = 8.2 Hz), 7.08 (d, 2H, J = 8.2 Hz), 5.01
(ddd, 1H, J = 2.1, 3.3, 9.8 Hz), 4.55 (ddd, 1H, J = 2.2, 3.3, 9.8 Hz),
3.17 (t, 1H, J = 8.6 Hz), 2.45–2.37 (m, 1H), 2.31 (s, 3H), 2.13 (dd,
1H, J = 5.1, 7.9 Hz), 2.04–1.09 (m, 2H), 1.77–1.65 (m, 4H), 1.63–
1.56 (m, 1H), 1.45 (t, 1H, J = 4.4 Hz), 1.39–1.26 (m, 3H), 1.17–1.16
(m, 1H), 1.04 (dd, 1H, J = 3.4, 13.8 Hz), 0.94 (s, 3H), 0.89 (s, 6H),
0.80 (s, 3H), 0.79 (s, 3H), 0.73 (s, 3H), 0.15 (dd, 1H, J = 3.5,
13.9 Hz);13C NMR (100 MHz, CDCl3, 25 °C, TMS): d 170.0, 166.9,
136.7, 131.6, 128.9 (two carbons), 129.2 (two carbons), 81.6,
81.3, 48.7, 48.3, 47.8, 47.4, 44.6, 44.4, 38.1, 36.7, 35.8, 31.4, 27.9,
27.3, 27.0, 26.8, 20.9, 19.6, 19.5, 18.7, 18.6, 18.4, 13.6, 13.4; GC–
MS (70 eV, EI): m/z (rel. int.): 492 (M+<1%), 356 (2), 185 (10), 137
(100), 136 (22), 95 (19), 81 (59), 69 (12). Anal. Calcd for
C32H44O4: C, 78.01; H, 9.00. Found: C, 78.17; H, 9.11.
4.6.5. Di-(ꢀ)-bornyl-(2R)-2-(4-chlorophenyl) cyclopropane-1,1-
dicarboxylate, 9b
Oil; ½a 2D5
ꢁ
¼ þ55:2 (c 1.30, CHCl3); 1H NMR (400 MHz, CDCl3,
25 °C, TMS): d 7.24 (d, 2H, J = 8.4 Hz), 7.15 (d, 2H, J = 8.4 Hz),
5.06 (ddd, 1H, J = 2.0, 3.5, 9.9 Hz), 4.54 (ddd, 1H, J = 2.0, 3.5,
9.9 Hz), 3.18 (t, 1H, J = 8.5 Hz), 2.38 (ddt, 1H, J = 3.5, 9.9,
13.6 Hz), 2.19 (ddt, 1H, J = 4.0, 9.8, 13.6 Hz), 2.12 (dd, 1H, J = 5.1,
8.5 Hz), 1.91–1.80 (m, 1H), 1.75–1.50 (m, 5H), 1.40–1.20 (m,
3H), 1.15–1.03 (m, 3H), 0.92 (s, 3H), 0.88 (s, 3H), 0.85 (s, 3H),
0.84 (dd, 1H, J = 3.5, 13.6 Hz), 0,78 (s, 6H), 0.36 (s, 3H); 13C NMR
(100 MHz, CDCl3, 25 °C, TMS): d 169.9, 166.6, 133.4, 133.2,
129.8 (two carbons), 128.4 (two carbons), 81.5, 81.4, 49.0, 48.5,
47.9, 47.7, 44.8, 44.6, 38.1, 36.2, 36.1, 31.0, 28.0, 27.9, 27.1,
26.8, 19.7, 19.6, 18.9, 18.8, 18.7, 13.5, 12.7; GC–MS (70 eV, EI):
m/z (rel. int.): 512 (M+<1%), 137 (100), 95 (17), 81 (60), 69 (11),
55 (5). Anal. Calcd for C31H41ClO4: C, 72.56; H, 8.05. Found: C,
73.01; H, 8.14.
4.6.9. Di-(ꢀ)-bornyl-(2R)-2-(4-methoxyphenyl)cyclopropane-1,
1-dicarboxylate, 9d
Oil; ½a 2D7
ꢁ
¼ þ53:5 (c 2.17, CHCl3); 1H NMR (400 MHz, CDCl3,
25 °C, TMS): d 7.15 (d, 2H, J = 8.7 Hz), 6.82 (d, 2H, J = 8.7 Hz), 5.07
(ddd, 1H, J = 2.1, 3.3, 9.9 Hz), 4.54 (ddd, 1H, J = 2.1, 3.3, 9.9 Hz),
3.78 (s, 3H), 3.20 (t, 1H, J = 8.5 Hz). 2.43–2.37 (m, 1H), 2.21–2.16
(m, 1H), 2.14 (dd, 1H, J = 5.0, 8.5 Hz), 1.96–1.89 (m, 1H), 1.78–
1.52 (m, 5H), 1.35–1.08 (m, 6H), 0.94 (s, 3H), 0.89 (s, 3H), 0.86 (s,
3H), 0.84 (dd, 1H, J = 3.6, 13.9 Hz), 0.79 (s, 3H), 0.78 (s, 3H), 0.40
(s, 3H); 13C NMR (100 MHz, CDCl3, 25 °C, TMS): d 170.3, 166.9,
158.9, 129.6 (two carbons), 126.8, 113.8 (two carbons), 81.2,
81.1, 55.3, 49.0, 48.5, 47.9, 47.6, 44.8, 44.6, 37.8, 36.3, 35.9, 31.4,
28.0, 27.8, 27.1, 26.8, 19.7, 19.6, 19.0, 18.8, 18.7, 13.5, 12.8; GC–
MS (70 eV, EI): m/z (rel. int.): 508 (M+<1%), 372 (2), 236 (11), 201
(10), 137 (100), 95 (17), 81 (69), 69 (13). Anal. Calcd for
C32H44O5: C, 75.56; H, 8.72. Found: C, 75.49; H, 8.84.
4.6.6. Di-(ꢀ)-bornyl-(2S)-2-(4-chlorophenyl) cyclopropane-1,1-
dicarboxylate, 10b
Oil; ½a 2D4
ꢁ
¼ ꢀ84:7 (c 1.26, CHCl3); 1H NMR (400 MHz, CDCl3,
25 °C, TMS): d 7.26 (d, 2H, J = 8.5 Hz) 7.19 (d, 2H, J = 8.5 Hz), 5,01
(ddd, 1H, J = 2.4, 3.9, 9.8 Hz), 4.57 (ddd, 1H, J = 2.4, 3.9, 9.8 Hz),
3.16 (t, 1H, J = 8.6 Hz), 2.40–2.37 (m, 1H), 2.10 (dd, 1H, J = 5.2,
7.7 Hz), 2.09–2.01 (m, 1H), 1.94–1.90 (m, 1H), 1.77–1.61 (m, 5H),
1.51 (t, 1H, J = 4.4 Hz), 1.34–1.16 (m, 3H), 1.02 (dd, 1H, J = 3.4,
13.8 Hz), 0.93 (s, 3H), 0.92–0.89 (m, 1H), 0.89 (s, 6H), 0.80 (s,
6H), 0.73 (s, 3H), 0,18 (dd, 1H, J = 3.5, 13.9 Hz); 13C NMR
(100 MHz, CDCl3, 25 °C, TMS): d 169.8, 166.7, 133.4, 133.1, 129.8
(two carbons), 128.4 (two carbons), 81.8, 81.6, 48.8, 48.4, 47.9,
47.5, 44.7, 44.4, 38.2, 36.7, 36.1, 31.0, 27.9, 27.5, 27.0, 26.9, 19.6,
19.5, 18.8, 18.7, 18.6, 13.6, 13.5; GC–MS (70 eV, EI): m/z (rel.
int.): (M+ 512< 1%), 137 (100), 95 (16), 81 (57), 69 (11), 55 (5);
Anal. Calcd for C31H41ClO4: C, 72.56; H, 8.05. Found: C, 72.64; H,
7.93.
4.6.10. Di-(ꢀ)-bornyl-(2S)-2-(4-methoxyphenyl)cyclopropane-1,
1-dicarboxylate, 10d
Oil; ½a 2D5
ꢁ
¼ ꢀ93:1 (c 2.88, CHCl3); 1H NMR (400 MHz, CDCl3,
25 °C, TMS): d 7.15 (d, 2H, J = 8.7 Hz), 6.83 (d, 2H, J = 8.7 Hz), 5.01
(ddd, 1H, J = 2.2, 3.1, 9.8 Hz), 4.55 (ddd, 1H, J = 2.1, 3.1, 9.8 Hz),
3.78 (s, 3H), 3.17 (t, 1H, J = 8.4 Hz), 2.44–2.35 (m, 1H), 2.11 (dd,
1H, J = 5.1, 7.9 Hz), 2.07–1.84 (m, 2H), 1.80–1.63 (m, 4H), 1.62–
1.54 (m, 1H), 1.47 (t, 1H, J = 4.4 Hz), 1.34–1.14 (m. 3H), 1.03 (dd,
1H, J = 3.4, 13.8 Hz), 0.93 (s, 3H), 0.89 (s, 6H), 0.88–0.85 (m, 1H),
0.80 (s, 3H), 0.79 (s, 3H), 0.73 (s, 3H), 0.17 (dd, 1H, J = 3.5,
13.8 Hz); 13C NMR (100 MHz, CDCl3, 25 °C, TMS): d 170.3, 167.1,
158.9, 129.5 (two carbons), 126.8, 113.8 (two carbons), 81.7,
81.4, 55.3, 48.8, 48.4, 47.9, 47.6, 47.7, 44.5, 38.1, 36.1, 35.7, 31.4,
27.9, 27.5, 27.1, 26.9, 19.7, 19.6, 18.8, 18.7, 18.6, 13.6, 13.5; GC-
MS (70 eV, EI): m/z (rel. int.): 508 (1), 372 (1), 236 (9), 201 (15),
137 (100), 95 (22), 81 (62), 69 (14). Anal. Calcd for C32H44O5: C,
75.56; H, 8.72. Found: C, 75.46; H, 8.65.
4.6.7. Di-(ꢀ)-bornyl-(2R)-2-(4-methylphenyl) cyclopropane-
1,1-dicarboxylate, 9c
Oil; ½a 2D6
ꢁ
¼ þ48:3 (c 2.16, CHCl3); 1H NMR (400 MHz, CDCl3,
25 °C, TMS): d 7.12 (d, 2H, J = 8.1 Hz), 7.07 (d, 2H, J = 8.1 Hz), 5,07
(ddd, 1H, J = 2.1, 3.4, 10.0 Hz), 4.54 (ddd, 1H, J = 2.1, 3.4, 10.0 Hz),
3.21 (t, 1H, J = 8.5 Hz), 2.34–2.37 (m, 1H), 2.30 (s, 3H), 2.22–2.18
(m, 1H), 2.16 (dd, 1H, J = 5.0, 8.5 Hz), 1.95–1.90 (m, 1H), 1.85–
1.55 (m, 5H), 1.37–1.22 (m, 3H), 1.19–1.08 (m, 3H), 0.94 (s, 3H),
0.89 (s, 3H), 0.90–0.80 (m, 1H), 0.87 (s, 3H), 0.79 (s, 3H), 0.78 (s,
4.6.11. Di-(ꢀ)-menthyl-2-hexylcyclopropane-1,1-dicarboxylate
1 diastereomer, 90f
Oil; ½a 2D1
ꢁ
¼ ꢀ15:7 (c 1.21, CHCl3); 1H NMR (400 MHz, CDCl3,
25 °C, TMS): d 4.73 (dt, 1H, J = 4.3, 10.9 Hz), 4.68 (dt, 1H, J = 4.3,

L. Bagnoli et al. / Tetrahedron: Asymmetry 20 (2009) 1506–1514
1513
10.8 Hz), 2.10–2.01 (m, 2H), 1.95 (dsept, 1H, J = 4.2, 6.9 Hz), 1.90–
1.78 (m. 2H), 1.74–1.62 (m, 4H), 1.61–1.20 (m, 16H), 1.10–0.95
(m, 4H), 0.94–0.85 (m, 17H), 0.74 (d, 6H, J = 6.9 Hz);13C NMR
(100 MHz, CDCl3, 25 °C, TMS): d 170.3, 168.0, 75.3, 75.2, 47.2,
46.8, 40.8, 40.7, 34.5, 34.3, 34.2, 31.6, 31.3 (two carbons), 28.9
(two carbons), 28.7, 27.8, 26.1, 25.7, 23.4, 22.9, 22.6, 22.1, 22.0,
20.9, 20.8, 20.7, 16.3, 15.8, 14.0; GC–MS (70 eV, EI): m/z (rel.
int.): 490 (M+<1%), 215 (63), 214 (78), 138 (49), 117 (23), 110
(54), 97 (20), 95 (27), 83 (100), 81 (33), 69 (37), 57 (27). Anal. Calcd
for C31H54O4: C, 75.87; H, 11.09. Found: C, 75.75; H, 11.23.
1.33 (m, 5H), 1.32–1.10 (m. 7H), 0.86 (t, 3H, J = 6.4 Hz);13C NMR
(100 MHz, CDCl3, 25 °C, TMS): d 170.9, 168.7, 52.5, 52.3, 33.8,
31.6, 28.9, 28.8, 28.7, 28.6, 22.5, 21.3, 13.9; GC–MS (70 eV, EI):
m/z (rel. int.): 242 (M+<1%), 211 (14), 179 (19), 153 (22), 145
(80), 132 (74), 121 (25), 113 (100), 108 (36), 95 (16), 81 (30), 67
(21), 59 (36). Anal. Calcd for C13H22O4: C, 64.44; H, 9.15. Found:
C, 64.12; H, 9.01.
4.7.6. 2 Dimethyl 2-hexylcyclopropane-1,1-dicarboxylate, ent-12f
Oil; ½a 2D2
¼ ꢀ49:0 (c 1.88, PhH). HPLC ((R,R) Whelk 01 (250 ꢂ 4.6
ꢁ
ID) eluant: hexane/i-PrOH 99.3:0.7, flow rate: 0.8 mL/min, UV
detection at 230 nm) tR 6.73 min. NMR and GC–MS are identical
to those of compound 12f. Anal. Calcd for C13H22O4: C, 64.44; H,
9.15. Found: C, 64.29; H, 9.28.
4.6.12. Di-(ꢀ)-menthyl-2-hexylcyclopropane-1,1-dicarboxylate
2 diastereomer, 100f
Oil; ½a 2D2
ꢁ
¼ ꢀ77:6 (c 2.48, CHCl3); 1H NMR (400 MHz, CDCl3,
25 °C, TMS): d 4.78 (dt, 1H, J = 4.4, 10.9 Hz), 4.76 (dt, 1H, J = 4.4,
10.9 Hz), 2.09 (dsept, 1H, J = 4.1, 6.8 Hz), 2.01–1.88 (m, 3H), 1.85–
1.75 (m, 1H), 1.73–1.60 (m, 4H), 1.55–1.15 (m, 17H), 1.13–0.96
(m, 4H), 0.93–0.85 (m, 16H), 0.78 (d, 3H, J = 6.9 Hz), 0.76 (d, 3H,
J = 6.9 Hz);13C NMR (100 MHz, CDCl3, 25 °C, TMS): d 170.2, 167.9,
75.2, 75.0, 47.2, 47.0, 40.9, 40.8, 34.4, 34.3, 34.2, 31.7, 31.4 (two car-
bons), 29.0, 28.9, 28.8, 28.7, 25.8, 25.3, 23.0, 22.7, 22.6, 22.0 (two
carbons), 21.2, 21.1, 20.9, 15.9, 15.6, 14.0; MS (70 eV, EI): m/z (rel.
int.): 490 (M+<1%), 215 (70), 214 (81), 138 (57), 117 (25), 110
(57), 97 (20), 95 (31), 83 (100), 81 (35), 69 (40), 57 (27). Anal. Calcd
forC31H54O4: C, 75.87; H, 11.09. Found: C, 75.72; H, 11.18.
4.8. Synthesis of cyclopropane diols
A solution of LiAlH4 2 M (1.5 mmol) in tetrahydrofuran was
added to cyclopropanes 9a,c,d,f and 10a,c,d,f (1 mmol) in anhy-
drous diethyl ether (10 mL) at 0 °C. The reaction mixtures were
then stirred for 3 h at room temperature. The reaction mixtures
were poured into an aqueous NH4Cl solution and extracted with
diethyl ether. The organic layers were dried over Na2SO4, filtered,
and evaporated under vacuum. Reaction products (Scheme 5) were
obtained in a pure form after column chromatography of the resi-
due on silica gel using a mixture of ethyl acetate and light petro-
leum (50:50) as eluant. The yields and the enantiomeric excesses
of compounds 13a,c,d,f and ent-13a,c,d,f are reported in Table 4.
The physical and spectroscopic data of compounds 13a,c,d,f and
ent-13a,c,d,f are reported below.
4.7. Synthesis of cyclopropane diesters
The synthesis of diesters 12a,b,f and ent-12a,b,f as reported in
Scheme 5 was carried out according to the procedure described
in the literature.12 The reaction products and the reaction yields
are reported in Table 4. The enantiomeric excesses were deter-
mined by chiral HPLC and are also reported in Table 4. The spectro-
scopic data of compounds 12a,13a–d ent-12a,13e and 12b,13a,b were
identical to those reported in the literature. Physical and spectro-
scopic data of compounds 12f and ent-12f are reported below.
4.8.1. [(2R)-2-Phenylcyclopropane-1,1-diyl]dimethanol, 13a
Mp 46–48 °C; ½a1D6 ¼ þ2:2 (c 1.75, CHCl3); 1H NMR (400 MHz,
CDCl3, 25 °C, TMS): d 7.27–7.11 (m, 5H), 3.75 (d, 1H, J = 11.3 Hz),
3.65 (d, 1H, J = 11.3 Hz), 3.53 (d, 1H, J = 11.7 Hz), 3.34 (d, 1H,
J = 11.7 Hz), 2.50 (br s, 1H), 2.23 (dd, 1H, J = 6.0, 8.4 Hz), 1.98 (br
s, 1H), 1.05 (dd, 1H, J = 5.4, 6.0 Hz), 0.92 (dd, 1H, J = 5.4,
8.4 Hz);13C NMR (100 MHz, CDCl3, 25 °C, TMS): d 137.6, 128.8
(two carbons), 128.2 (two carbons), 126.3, 69.8, 65.0, 30.6, 26.7,
12.9; MS (70 eV, EI): m/z (rel. int.): 178 (1), 129 (91), 115 (33),
104 (100), 91 (62), 78 (27). Anal. Calcd for C11H14O2: C, 74.13; H,
7.92. Found: C, 74.27; H, 7.82.
4.7.1. Dimethyl (2R)-2-phenylcyclopropane-1,1-dicarboxylate,
12a
Oil; ½a 2D3
ꢁ
¼ þ121:7 (c 1.62, PhH).13a–c HPLC (Chiracel OD-H col-
umn (250 ꢂ 4.6 ID) eluant: hexane/i-PrOH 99:1, flow rate: 0.6 mL/
min, UV detection at 230 nm) tR 20.86 min.
4.7.2. Dimethyl (2S)-2-phenylcyclopropane-1,1-dicarboxylate,
ent-12a
4.8.2. [(2S)-2-Phenylcyclopropane-1,1-diyl]dimethanol, ent-13a
Mp 44–48 °C; ½a 1D8
¼ ꢀ2:1 (c 2.39, CHCl3). Anal. Calcd for
ꢁ
Mp 61–62 °C; ½a 2D1
ꢁ
¼ ꢀ114:3 (c 2.22, PhH).13c,e HPLC (Chiracel
C11H14O2: C, 74.13; H, 7.92. Found: C, 74.30; H, 7.91.
OD-H column (250 ꢂ 4.6 ID) eluant: hexane/i-PrOH 99:1, flow rate:
0.6 mL/min, UV detection at 230 nm) tR 19.50 min.
4.8.3. [(2R)-2-(4-Methylphenyl)cyclopropane-1,1-
diyl]dimethanol, 13c
4.7.3. Dimethyl (2R)-2-(4-chlorophenyl)cyclopropane-1,1-dicar-
Mp 40–42 °C; ½a 2D3
¼ þ9:9 (c 1.41, CHCl3). HPLC(ChiralpackAD-H
ꢁ
boxylate, 12b
column (250 ꢂ 4.6 ID), eluant: hexane/i-PrOH 96:4, flow rate:
0.8 mL/min, UV detection at 230 nm) tR 39.02 min. 1H NMR
(400 MHz, CDCl3, 25 °C, TMS): d 7.17 (d, 2H, J = 7.1 Hz), 7.12 (d, 2H,
J = 7.1 Hz), 3.81 (d, 1H, J = 11.2 Hz), 3.72 (d, 1H, J = 11.2 Hz), 3.62
(d, 1H, J = 11.6 Hz), 3.40 (d, 1H, J = 11.6 Hz), 2.34 (s, 3H), 2.26 (dd,
1H, J = 6.3, 8.1 Hz), 1.92 (br s, 2H), 1.08 (t, 1H, J = 5.8 Hz), 0.96 (dd,
1H, J = 5.4, 8.1 Hz);13C NMR (100 MHz, CDCl3, 25 °C, TMS): d 136.0,
134.5, 129.1 (two carbons), 128.7 (two carbons), 70.2, 65.5, 30.6,
26.4, 20.9, 12.9; GC–MS (70 eV, EI): m/z (rel. int.): 192 (5), 161
(14), 143 (100), 128 (59), 118 (57), 105 (48), 91 (34), 77 (15). Anal.
Calcd for C12H16O2: C, 74.97; H, 8.39. Found: C, 74.86; H, 8.45.
Oil; ½a 2D1
ꢁ
¼ þ123:3 (c 1.28, PhH).13a–b,f HPLC (Chiracel OD-H col-
umn (250 ꢂ 4.6 ID) eluant: hexane/i-PrOH 99:1, flow rate: 0.8 mL/
min, UV detection at 230 nm) tR 16.24 min.
4.7.4. Dimethyl (2S)-2-(4-chlorophenyl)cyclopropane-1,1-dicar-
boxylate, ent-12b
Oil; ½a 2D1
¼ ꢀ117:2 (c 1.23, PhH). HPLC (Chiracel OD-H column
ꢁ
(250 ꢂ 4.6 ID) eluant: hexane/i-PrOH 99:1, flow rate: 0.8 mL/min,
UV detection at 230 nm) tR 15.08 min.
4.7.5. Dimethyl 2-hexylcyclopropane-1,1-dicarboxylate 12f
Oil; ½a 2D1
ꢁ
¼ þ53:0 (c 1.94, PhH). HPLC ((R,R) Whelk 01 (250 ꢂ 4.6
4.8.4. [(2S)-2-(4-Methylphenyl)cyclopropane-1,1-diyl]dimeth-
anol, ent-13c
ID), eluant: hexane/i-PrOH 99.3:0.7, flow rate: 0.8 mL/min, UV
detection at 230 nm) tR 6.97 min. 1H NMR (400 MHz, CDCl3,
25 °C, TMS): d 3.74 (s, 3H), 3.71 (s, 3H), 1.92–1.83 (m, 1H), 1.50–
Mp 38–40 °C; ½a 2D5
¼ ꢀ8:6 (c 2.42, CHCl3). HPLC (Chiralpack AD-
ꢁ
H column (250 ꢂ 4.6 ID), eluant: hexane/i-PrOH 96:4, flow rate:

1514
L. Bagnoli et al. / Tetrahedron: Asymmetry 20 (2009) 1506–1514
0.8 mL/min, UV detection at 230 nm) tR 42.82 min. Anal. Calcd for
4.9.1. Methyl (1S,2R)-1-[(tert-butoxycarbonyl)amino]-2-phenyl-
C12H16O2: C, 74.97; H,8.39. Found: C, 74.83; H, 8.36.
cyclopropanecarboxylate 14a
Oil; ½a 2D1
ꢁ
¼ ꢀ80:5 (c 1.82, CHCl3).13c
4.8.5. [(2R)-2-(4-Methoxyphenyl)cyclopropane-1,1-diyl]dime-
4.9.2. Methyl (1R,2S)-1-[(tert-butoxycarbonyl)amino]-2-phenyl-
cyclopropanecarboxylate ent-14a
thanol, 13d
Mp 84–88 °C; ½a 3D0
¼ þ9:1 (c 1.75, CHCl3). HPLC (Chiralpack AD-
ꢁ
Oil; ½a 2D5
ꢁ
¼ ꢀ79:2 (c 1.35, CHCl3).13c
H column (250 ꢂ 4.6 ID), eluant: hexane/i-PrOH 90:10, flow rate:
1 mL/min, UV detection at 230 nm) tR 14.19 min. 1H NMR
(400 MHz, CDCl3, 25 °C, TMS): d 7.17 (d, 2H, J = 8.5 Hz), 6.82 (d,
2H, J = 8.5 Hz), 3.79 (d, 1H, J = 11.2 Hz), 3.78 (s, 3H), 3.68 (d, 1H,
J = 11.2 Hz), 3.58 (d, 1H, J = 11.6 Hz), 3.37 (d, 1H, J = 11.6 Hz), 2.75
(br s, 1H), 2.21 (dd, 1H, J = 6.2, 8.5 Hz), 1.75 (br s, 1H), 1.01 (t,
1H, J = 5.6 Hz), 0.93 (dd, 1H, J = 5.5, 8.5 Hz);13C NMR (100 MHz,
CDCl3, 25 °C, TMS): d 158.1, 129.8 (two carbons), 129.5, 113.7
(two carbons), 70.2, 65.5, 55.2, 30.4, 25.9, 13.0; GC–MS (70 eV,
EI): m/z (rel. int.): 208 (23), 177 (51), 159 (100), 144 (59), 121
(56), 91 (33), 77 (19). Anal. Calcd for C12H16O3: C, 69.21; H, 7.74.
Found: C, 69.17; H, 7.83.
Acknowledgments
Financial support from MIUR, National Projects PRIN2005, and
PRIN2007, University of Perugia and Consorzio CINMPIS is grate-
fully acknowledged.
References
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4.8.6. [(2S)-2-(4-Methoxyphenyl)cyclopropane-1,1-diyl]
dimethanol, ent-13d
Mp 86–90 °C; ½a 2D7
ꢁ
¼ ꢀ9:4 (c 1.21, CHCl3). HPLC (Chiralpack AD-
4. (a) Lebel, H.; Marcoux, J. F.; Molinaro, C.; Charette, A. B. Chem. Rev. 2003, 103,
977; (b) Reissig, H. U.; Zimmer, R. Chem. Rev. 2003, 103, 1151.
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Ando, R.; Sugawara, T.; Shimizu, M.; Kuwajima, I. Bull. Chem. Soc. Jpn. 1984, 57,
2897; (c) Shimizu, M.; Kuwajima, I. J. Org. Chem. 1980, 45, 2921; (d) Tiecco, M.;
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(b) Tiecco, M.; Testaferri, L.; Bagnoli, L.; Scarponi, C.; Temperini, A.; Marini, F.;
Santi, C. Tetrahedron: Asymmetry 2007, 18, 2758; (c) Tiecco, M.; Testaferri, L.;
Temperini, A.; Bagnoli, L.; Marini, F.; Santi, C. Chem. Eur. J. 2004, 10, 1752; (d)
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C. Synthesis 2005, 579.
H column (250 ꢂ 4.6 ID), eluant: hexane/i-PrOH 90:10, flow rate:
1 mL/min, UV detection at 230 nm) tR 16.09 min. Anal. Calcd for
C12H16O3: C, 69.21; H, 7.74. Found: C, 69.16; H, 7.67.
4.8.7. (2-Hexylcyclopropane-1,1-diyl)dimethanol (from 1 dias-
tereomer), 13f
Oil; ½a 2D1
ꢁ
¼ þ35:8 (c 2.3, CHCl3); 1H NMR (400 MHz, CDCl3,
25 °C, TMS): d 3.82 (d, 1H, J = 11.4 Hz), 3.71 (d, 1H, J = 11.4 Hz),
3.57 (d, 1H, J = 11.1 Hz), 3.52 (d, 1H, J = 11.1 Hz), 2.78 (br s, 2H),
1.55–1.47 (m, 1H), 1.43–1.19 (m, 9H), 0.88 (t, 3H, J = 6.7 Hz),
0.85–0.72 (m, 1H), 0.60 (dd, 1H, J = 4.8, 8.5 Hz), 0.21 (t, 1H,
J = 5.2 Hz); 13C NMR (100 MHz, CDCl3, 25 °C, TMS): d 71.2, 65.7,
31.8, 30.0, 29.1, 28.9, 27.6, 22.7, 22.6, 14.8, 14.0; MS (70 eV, EI):
m/z (rel. int.): 186 (M+<1%), 130 (100), 129 (62), 115 (15), 75
(14). Anal. Calcd for C11H22O2: C, 70.92; H, 11.90. Found: C,
70.76; H, 11.69.
7. Prakash Das, J.; Roy, S. J. Org. Chem. 2002, 67, 7861.
8. Kuang, C.; Yang, Q.; Senboku, H.; Tokuda, M. Tetrahedron 2005, 61, 4043.
9. (a) Perin, G.; Lenardão, E. J.; Jacob, R. G.; Panatieri, R. B. Chem. Rev. 2009, 109,
1277. and references cited therein; (b) Raucher, S.; Hansen, M. R.; Colter, M. A. J.
Org. Chem. 1978, 43, 4885; (c) Silveira, C. C.; Begnini, M. L.; Boeck, P.; Braga, A. L.
Synthesis 1997, 221.
10. (a) Tiecco, M.; Testaferri, L.; Tingoli, M.; Chianelli, D.; Montanucci, M.
Tetrahedron Lett. 1984, 25, 4975; (b) Testaferri, L.; Tiecco, M.; Tingoli, M.;
Chianelli, D. Tetrahedron 1985, 41, 1401.
11. Zhang, Y.; Shibatomi, K.; Yamamoto, H. J. Am. Chem. Soc. 2004, 126, 15038.
12. Yamazaki, S.; Kataoka, H.; Yamabe, S. J. Org. Chem. 1999, 64, 2367.
13. (a) Kang, Y.-B.; Sun, X.-L.; Tang, Y. Angew. Chem., Int. Ed. 2007, 46, 3918; (b)
Muller, P.; Ghanem, A. Org. Lett. 2004, 6, 4347; (c) Davies, H. M. L.; Bruzinski, P.
R.; Lake, D. H.; Kong, N.; Fall, M. J. J. Am. Chem. Soc. 1996, 118, 6897; (d) Muller,
P.; Allenbach, Y.; Robert, E. Tetrahedron: Asymmetry 2003, 14, 779; (e) Corey, E.
J.; Gant, T. G. Tetrahedron Lett. 1994, 35, 5373; (f) Sato, M.; Hisamichi, H.;
Kaneko, C. Tetrahedron Lett. 1989, 30, 5281.
14. (a) Wurz, R. P.; Charette, A. B. J. Org. Chem. 2004, 69, 1262. and references cited
therein; (b) Adams, L. A.; Aggarwal, V. K.; Bonnert, R. V.; Bressel, B.; Cox, R. J.;
Shepherd, J.; De Vicente, J.; Walter, M.; Whittingham, W. G.; Winn, C. L. J. Org.
Chem. 2003, 68, 9433. and references cited therein.
4.8.8. (2-Hexylcyclopropane-1,1-diyl)dimethanol (from 2 dias-
tereomer), ent-13f
Oil; ½a 2D1
¼ ꢀ33:8 (c 2.3, CHCl3); Anal. Calcd for C11H22O2: C,
ꢁ
70.92; H, 11.90. Found: C, 71.09; H, 11.97.
4.9. Synthesis of cyclopropane a-amino acids (ACCs)
15. Cativiela, C.; Diaz-de-Villegas, M. D. Tetrahedron: Asymmetry 2000, 11, 645.
16. (a) Burgess, K.; Lim, D.; Ho, K.-K.; Ke, C.-Y. J. Org. Chem. 1994, 59, 2179; (b)
Cativiela, C.; Diaz-de-Villegas, M. D.; Jimenez, A. I.; Lopez, P.; Marraud, M.;
Oliveros, L. Chirality 1999, 11, 583.
17. (a) Williams, R. M. Synthesis of Optically Active Amino Acids; Pergamon Press:
Oxford, 1989; (b) Spatola, A. F. In Chemistry and Biochemistry of Amino Acids,
Peptides, and proteins; Weinstein, B., Ed.; Marcel Dekker: New York, 1983; p 7,
267.
The synthesis of ACCs 14a and ent-14a reported in Scheme 6
was effected according to the procedure described in the litera-
ture.13c,16a The reaction products and the reaction yields are re-
ported in Scheme 6. The physical and spectroscopic data are
identical to those reported in the literature.13c,16b